Conformational dynamics and multimodal interaction of Paxillin with the focal adhesion targeting domain
Contact us if these videos are not relevant.
Contact us if these videos are not relevant.
View abstract on PubMed
Summary
This summary is machine-generated.Paxillin (PXN) and focal adhesion kinase (FAK) form a complex essential for cell migration. Binding causes PXN compaction into multiple states, revealing how cellular networks are rewired for phenotypic changes.
Area Of Science
- Cell biology
- Structural biology
- Biochemistry
Background
- Paxillin (PXN) and focal adhesion kinase (FAK) are key components of focal adhesions.
- PXN acts as a scaffold, recruiting proteins that regulate cell migration and survival.
- The interaction between PXN and FAK is crucial for FAK localization to focal adhesions.
Purpose Of The Study
- To elucidate the structural basis of the interaction between the PXN N-domain and the FAK FAT domain.
- To understand how this interaction influences the dynamics and function of the focal adhesion complex.
- To provide insights into how cellular networks are rewired through structural changes in hub proteins.
Main Methods
- The study likely employed biophysical techniques (e.g., NMR, X-ray crystallography, cryo-EM) to determine the structure of the PXN-FAT complex.
- Computational methods were likely used to analyze the flexibility and interconverting states of the complex.
- Bioinformatic analyses were used to assess the conservation of key contacts.
Main Results
- The PXN N-domain undergoes significant compaction upon binding to the FAK FAT domain.
- A 48-kilodalton multimodal complex is formed with four major interconverting states.
- Each state exhibits unique contacts involving disordered regions, which are conserved and highly represented.
Conclusions
- The findings provide a structural foundation for understanding PXN-mediated signaling.
- Shifts in the multistate equilibrium of the PXN-FAT complex can rewire cellular networks.
- This mechanism contributes to phenotypic changes, offering insights into cell migration and survival regulation.
Contact us if these videos are not relevant.
Contact us if these videos are not relevant.
Related Concept Videos
Integrins act both as extracellular input receivers and as intracellular processing activators. As their name suggests, integrins are entirely integrated into the membrane structure. Their hydrophobic membrane-spanning regions interact with the phospholipid bilayer's hydrophobic region. These membrane receptors provide extracellular attachment sites for effectors like hormones and growth factors. They activate intracellular response cascades when their effectors are bound and active.
Some...
Multiprotein signaling complexes are formed in a dynamic process involving protein-protein interactions at the cytoplasmic domain of transmembrane receptors or enzymatic and non-enzymatic proteins associated with the receptor. These complexes ensure the activation and propagation of intracellular signals that regulate cell functions.
Interaction domains in cell signaling
Interaction domains recognize exposed features of their binding partners containing post-translationally modified sequences,...
The adherens junctions that anchor cells together are multi-protein complexes that dynamically adapt to mechanical stimuli such as tensile forces and shear stress. Mechanosensory proteins in these junctions can sense such mechanical stimuli and undergo a shift in their conformation, resulting in an altered function — a process called mechanotransduction.
α-Catenin as a Mechanosensory Protein
The α-catenin of adherens junctions is an allosteric protein with three VH (vinculin...
Cells migrating in response to external stimuli form lamellipodia, which are thin membrane protrusions supported by a mesh of linked, branched, or unbranched actin filaments. These actin filaments interact with myosin motor proteins, creating the dynamic actomyosin complex within the cytoskeleton. Contractility, or the ability to generate contractile stress, is inherent to the actomyosin complex. It helps cells detect the stiffness of the surrounding ECM and exert contractile force for...
Filopodia are thin, actin-rich cellular protrusions that play an important role in many fundamental cellular functions. They vary in their occurrence, length, and positioning in different cell types, suggesting their diverse roles.
Their main function is to guide migrating cells during normal tissue morphogenesis or cancer metastasis by recognizing and making initial contacts with the extracellular matrix. However, they can also act as stationary cell anchors or help to establish communication...
Catenins are characterized by multiple binding domains and dynamic structures that allow them to function as linker proteins in cell junction complexes. All catenins, except α-catenin, contain a characteristic protein sequence called the armadillo repeat and are therefore also called armadillo proteins.
Catenins in Cell Junctions
Catenins bind to cell adhesion molecules such as cadherins and link them to different cytoskeletal proteins depending on the type of cell junction. At the...